Is DSPP p.Ser845Arg (c.2535C>A) pathogenic?

DSPP p.Ser845Arg (c.2535C>A) is classified Likely benign in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-12-10). AlphaMissense: ambiguous (0.536); Low-frequency (popmax 3.75%, afr).

How common is DSPP p.Ser845Arg (c.2535C>A) in the general population?

DSPP p.Ser845Arg (c.2535C>A) is low-frequency (popmax 3.75%, afr) (gnomAD).

What do computational predictors say about DSPP p.Ser845Arg (c.2535C>A)?

AlphaMissense predicts ambiguous (score 0.536) — an in-silico prediction, not a clinical call.

DSPP p.Ser845Arg

c.2535C>A · rs367568852 · VCV1198805

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.536 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.75%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.536	ambiguous
REVEL	0.232	benign-leaning
SaProt	LLR -11.68	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -11	GERP -1.4
Regional constraint	o/e 0.73	unconstrained · MANE · 1,389 bp · p 1.3e-11 · regional, not allelic
Overall
CADD	4.926	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.75% African / African-American · 2,659/70,930 alleles

Filtering AF 3.63% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.58%

Overall 0.2% 3,020/1,509,302 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.75%	27
Admixed American	0.288%	348
Remaining individualsnot grpmax-eligible	0.267%	375
Middle Eastern	0.12%	830
South Asian	0.0112%	8,933
European (non-Finnish)	0.00464%	21,571

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DSPP
Protein: p.Ser845Arg
Coding: c.2535C>A
dbSNP: rs367568852
Type: single nucleotide variant
Location: chr4:87615197 (GRCh38)

Full DSPP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dspp-p-ser845arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown